Coupling changes in cell shape to chromosome segregation

Animal cells undergo dramatic changes in shape, mechanics and polarity as they progress through the different stages of cell division. These changes begin at mitotic entry, with cell–substrate adhesion remodelling, assembly of a cortical actomyosin network and osmotic swelling, which together enable cells to adopt a near spherical form even when growing in a crowded tissue environment. These shape changes, which probably aid spindle assembly and positioning, are then reversed at mitotic exit to restore the interphase cell morphology. Here, we discuss the dynamics, regulation and function of these processes, and how cell shape changes and sister chromatid segregation are coupled to ensure that the daughter cells generated through division receive their fair inheritance

Differential regulation of cell death pathways by the microenvironment correlates with chemoresistance and survival in leukaemia

Glucocorticoids (GCs) and topoisomerase II inhibitors are used to treat acute lymphoblastic leukaemia (ALL) as they induce death in lymphoid cells through the glucocorticoid receptor (GR) and p53 respectively. Mechanisms underlying ALL cell death and the contribution of the bone marrow microenvironment to drug response/resistance remain unclear. The role of the microenvironment and the identification of chemoresistance determinants were studied by transcriptomic analysis in ALL cells treated with Dexamethasone (Dex), and Etoposide (Etop) grown in the presence or absence of bone marrow conditioned media (CM). The necroptotic (RIPK1) and the apoptotic (caspase-8/3) markers were downregulated by CM, whereas the inhibitory effects of chemotherapy on the autophagy marker Beclin-1 (BECN1) were reduced suggesting CM exerts cytoprotective effects. GCs upregulated the RIPK1 ubiquitinating factor BIRC3 (cIAP2), in GC-sensitive (CEM-C7-14) but not in resistant (CEM-C1-15) cells. In addition, CM selectively affected GR phosphorylation in a site and cell-specific manner. GR is recruited to RIPK1, BECN1 and BIRC3 promoters in the sensitive but not in the resistant cells with phosphorylated GR forms being generally less recruited in the presence of hormone. FACS analysis and caspase-8 assays demonstrated that CM promoted a pro-survival trend. High molecular weight proteins reacting with the RIPK1 antibody were modified upon incubation with the BIRC3 inhibitor AT406 in CEM-C7-14 cells suggesting that they represent ubiquitinated forms of RIPK1. Our data suggest that there is a correlation between microenvironment-induced ALL proliferation and altered response to chemotherapy

The value of systematic pattern analysis in FNAC of breast lesions: 225 cases with cytohistological correlation

Background : Fine needle aspiration cytology (FNAC) has a high rating in the assessment of breast lesions. Various methods have been used to diagnose cytology of breast lesions. Aims : Present study was undertaken to evaluate the feasibility of application of systematic pattern analysis based on morphology in diagnosing breast aspirates. Materials and Methods : This is a retrospective study of FNAC of the breast done over a period of 4 years in a tertiary care centre. A total of 225 cases of breast lesions for which FNAC was done with histological follow-up were included in the study. Breast aspirates were provisionally diagnosed based on systematic pattern analysis. Aspirates were grouped into six categories based on predominant cellular pattern, and correlation between cytological and histological diagnosis was assessed. Results : Application of pattern analysis on FNAC of breast lesions in our study had a sensitivity of 94.5%, specificity of 98%, diagnostic accuracy of 97%, positive predictive value of 95.8%, and negative predictive value of 97.4%. Conclusions : Systematic pattern analysis based on morphology of FNAC smears was found to be highly reliable and could be easily reproducible in the assessment of breast masses